The neural retina is the sole light-sensing tissue in mammals, which meditates image and non-image forming pathways controlling aspects of human physiology. Vision, from an evolutionary aspect, has enabled humans to hunt and gather resources, as well as, protect themselves from natural dangers by keen visual observations of their immediate environment. However, non-image forming visual pathways have recently started to be elucidated but are still poorly understood. The broad scope of this project is to expound on the idea that light history can directly affect retinal function, thereby altering its signaling to the brain. Our research group has published work which established that differential photoperiods have sustained effects on biological circadian rhythms and mouse behavior (Ciarleglio et al., 2011). Also, it is well known that humans with seasonal affective disorder (SAD) display altered mood (i.e., depression) during extreme changes in lighting environment. Published data shows that humans diagnosed with SAD have altered retinal responses when assessed by electroretinographic techniques (Hebert et al., 2002; A-M et al., 2011). Taken together, we hypothesize that light history has an effect on retinal function, ultimately mediated by changes in retinal gene transcription and protein expression. Addressing this question could expose a link between alterations in retinal function and SAD, especially since previous research has shown that a missense mutation in the melanopsin gene could predispose humans to SAD (Roecklein, K.A., et al., 2009). Recently, it was also shown that the melanopsin system in zebrafish is responsive to alterations in photoperiod (Matos-Cruz, V. et al., 2011). These data provide compelling evidence that light history affects retinal function. PUBLIC HEALTH RELEVANCE: It has been established that humans with Seasonal Affective Disorder during the winter months and animals subject to changes in lighting environment have altered retinal responses (Gagni, A-M et al., 2011; Lavoie, M-P et al., 2009; Hebert, M. et al., 2002; Cruz, V-C et al., 2011). Unfortunately, the retinal neurobiology underlying these altered electrical activities in response to light history is ambiguous. Therefore, an in-depth examination of mammalian retinal response to altered light history could potentially provide novel, more specific cellular and molecular targets reactive to light exposure, identifying the retina's involvement in light-sensitive mood behaviors.